The quenching of cluster satellite galaxies is inextricably linked to the suppression of their cold interstellar medium (ISM) by environmental mechanisms. While the removal of neutral atomic hydrogen (H i) at large radii is well studied, how the environment impacts the remaining gas in the centres of galaxies, which are dominated by molecular gas, is less clear. Using new observations from the Virgo Environment traced in CO survey (VERTICO) and archival H i data, we study the H i and molecular gas within the optical discs of Virgo cluster galaxies on 1.2-kpc scales with spatially resolved scaling relations between stellar ( $\Sigma_{\star}$ ), H i ( $\Sigma_{\text{H}\,{\small\text{I}}}$ ), and molecular gas ( $\Sigma_{\text{mol}}$ ) surface densities. Adopting H i deficiency as a measure of environmental impact, we find evidence that, in addition to removing the H i at large radii, the cluster processes also lower the average $\Sigma_{\text{H}\,{\small\text{I}}}$ of the remaining gas even in the central $1.2\,$ kpc. The impact on molecular gas is comparatively weaker than on the H i, and we show that the lower $\Sigma_{\text{mol}}$ gas is removed first. In the most H i-deficient galaxies, however, we find evidence that environmental processes reduce the typical $\Sigma_{\text{mol}}$ of the remaining gas by nearly a factor of 3. We find no evidence for environment-driven elevation of $\Sigma_{\text{H}\,{\small\text{I}}}$ or $\Sigma_{\text{mol}}$ in H i-deficient galaxies. Using the ratio of $\Sigma_{\text{mol}}$ -to- $\Sigma_{\text{H}\,{\small\text{I}}}$ in individual regions, we show that changes in the ISM physical conditions, estimated using the total gas surface density and midplane hydrostatic pressure, cannot explain the observed reduction in molecular gas content. Instead, we suggest that direct stripping of the molecular gas is required to explain our results.

Non-communicable diseases (NCD) such as CVD and type 2 diabetes mellitus are major contributors to the burden of disease. NCD are largely driven by modifiable lifestyle factors including poor diet and insufficient physical activity, and consequently, prevention is a public health priority. Although diet and physical activity levels can be improved via lifestyle interventions, long-term adherence to such interventions remains low, which limits their effectiveness. Thus, it is critical to identify the underlying mechanisms that challenge uptake and adherence to such interventions. The current commentary discusses an important, but underexplored, psychological driver of poor adherence to lifestyle interventions, namely, future discounting, which describes the tendency to prefer smaller, short-term rewards over larger, long-term rewards. For example, in the nutrition domain, future discounting refers to valuing the immediate reward of excessive intake of energy-dense, nutrient-poor, discretionary foods high in salt, sugar, and saturated fat, and insufficient intake of low-energy, nutrient-dense, whole foods such as vegetables. Prominent theoretical models propose that excessive future discounting is a major contributor to the development of unhealthy lifestyle behaviours. Furthermore, a vast body of evidence suggests that future discounting plays a key role in risk of NCD. Thus, the evidence to date supports the idea that future discounting is an important multi-behaviour target for supporting lifestyle behaviour change; however, this approach has been largely neglected in preventive health efforts. Furthermore, this commentary discusses promising techniques (e.g. Episodic Future Thinking) for disrupting future discounting to promote improved adherence to lifestyle interventions aimed at reducing NCD risk.

Genes associated with educational attainment may be related to or interact with adolescent alcohol, tobacco and cannabis use. Potential gene–environment interplay between educational attainment polygenic scores (EA-PGS) and adolescent alcohol, tobacco, and cannabis use was evaluated with a series of regression models fitted to data from a sample of 1871 adult Australian twins. All models controlled for age, age2, cohort, sex and genetic ancestry as fixed effects, and a genetic relatedness matrix was included as a random effect. Although there was no evidence that adolescent alcohol, tobacco or cannabis use interacted with EA-PGS to influence educational attainment, there was a significant, positive gene–environment correlation with adolescent alcohol use at all PGS thresholds (ps <.02). Higher EA-PGS were associated with an increased likelihood of using alcohol as an adolescent (ΔR2 ranged from 0.5% to 1.1%). The positive gene–environment correlation suggests a complex relationship between educational attainment and alcohol use that is due to common genetic factors.

Worldwide type 2 diabetes (T2D) prevalence is increasing dramatically. The present study aimed to evaluate the association between dietary habits and T2D in an Iranian adult population using a cross-sectional analysis of the Shahedieh cohort study. Participants were adults aged 35–70 years (n 9261) from Zarch and Shahedieh, Yazd, Iran, who attended the baseline phase of the Shahedieh cohort study. Dietary habits including meal frequency, fried-food consumption, adding salt to prepared meals and grilled-food consumption were assessed by a standard questionnaire. T2D was defined as fasting plasma glucose (FPG) ≥126 mg/dl according to the American Diabetes Association. Multiple logistic regression assessed the association between dietary habits and T2D. Individuals who consumed a meal more than six times per day compared to three times per day had greater odds for T2D (OR 2⋅503, 95 % CI 1⋅651, 3⋅793). These associations remained significant in a fully adjusted model. There was a significant association between greater intakes of fried foods and prevalence of T2D (OR 1⋅294, 95 % CI 1⋅004, 1⋅668) in the adjusted model. No significant associations were observed between other dietary habits (adding salt to prepared meals and grilled-food consumption) and odds of T2D in all crude and adjusted models. In conclusion, we have highlighted the association between meal and fried-food consumption frequencies with risk of T2D. Large longitudinal studies in different ethnicities are needed to confirm these associations.

The coronavirus disease 2019 (COVID-19) pandemic has placed significant burden on healthcare systems. We compared Clostridioides difficile infection (CDI) epidemiology before and during the pandemic across 71 hospitals participating in the Canadian Nosocomial Infection Surveillance Program. Using an interrupted time series analysis, we showed that CDI rates significantly increased during the COVID-19 pandemic.

Research among non-industrial societies suggests that body kinematics adopted during running vary between groups according to the cultural importance of running. Among groups in which running is common and an important part of cultural identity, runners tend to adopt what exercise scientists and coaches consider to be good technique for avoiding injury and maximising performance. In contrast, among groups in which running is not particularly culturally important, people tend to adopt suboptimal technique. This paper begins by describing key elements of good running technique, including landing with a forefoot or midfoot strike pattern and leg oriented roughly vertically. Next, we review evidence from non-industrial societies that cultural attitudes about running associate with variation in running techniques. Then, we present new data from Tsimane forager–horticulturalists in Bolivia. Our findings suggest that running is neither a common activity among the Tsimane nor is it considered an important part of cultural identity. We also demonstrate that when Tsimane do run, they tend to use suboptimal technique, specifically landing with a rearfoot strike pattern and leg protracted ahead of the knee (called overstriding). Finally, we discuss processes by which culture might influence variation in running techniques among non-industrial societies, including self-optimisation and social learning.

Individuals with discordantly high apoB to LDL-cholesterol levels carry a higher risk of atherosclerotic CVD compared with those with average or discordantly low apoB to LDL-cholesterol. We aimed to determine associations between apoB and LDL-cholesterol discordance in relation to nutrient patterns (NP) using National Health and Nutrition Examination Survey data. Participants were grouped by established LDL-cholesterol and apoB cut-offs (Group 1: low apoB/low LDL-cholesterol, Group 2: low apoB/high LDL-cholesterol, Group 3: high apoB/low LDL-cholesterol, Group 4: high apoB/high LDL-cholesterol). Principle component analysis was used to define NP. Machine learning (ML) and structural equation models were applied to assess associations of nutrient intake with apoB/LDL-cholesterol discordance using the combined effects of apoB and LDL-cholesterol. Three NP explained 63·2 % of variance in nutrient consumption. These consisted of NP1 rich in SFA, carbohydrate and vitamins, NP2 high in fibre, minerals, vitamins and PUFA and NP3 rich in dietary cholesterol, protein and Na. The discordantly high apoB to LDL-cholesterol group had the highest consumption of the NP1 and the lowest consumption of the NP2. ML showed nutrients that had the greatest unfavourable dietary contribution to individuals with discordantly high apoB to LDL-cholesterol were total fat, SFA and thiamine and the greatest favourable contributions were MUFA, folate, fibre and Se. Individuals with discordantly high apoB in relation to LDL-cholesterol had greater adherence to NP1, whereas those with lower levels of apoB, irrespective of LDL-cholesterol, were more likely to consume NP3.

We propose a fully distributed actor-critic architecture, named diffusion-distributed-actor-critic Diff-DAC, with application to multitask reinforcement learning (MRL). During the learning process, agents communicate their value and policy parameters to their neighbours, diffusing the information across a network of agents with no need for a central station. Each agent can only access data from its local task, but aims to learn a common policy that performs well for the whole set of tasks. The architecture is scalable, since the computational and communication cost per agent depends on the number of neighbours rather than the overall number of agents. We derive Diff-DAC from duality theory and provide novel insights into the actor-critic framework, showing that it is actually an instance of the dual-ascent method. We prove almost sure convergence of Diff-DAC to a common policy under general assumptions that hold even for deep neural network approximations. For more restrictive assumptions, we also prove that this common policy is a stationary point of an approximation of the original problem. Numerical results on multitask extensions of common continuous control benchmarks demonstrate that Diff-DAC stabilises learning and has a regularising effect that induces higher performance and better generalisation properties than previous architectures.

Background: Healthcare services are increasingly shifting from inpatient to outpatient settings. Outpatient settings such as emergency departments (EDs), oncology clinics, dialysis clinics, and day surgery often involve invasive procedures with the risk of acquiring healthcare-associated infections (HAIs). As a leading cause of HAI, Clostridioides difficile infection (CDI) in outpatient settings has not been sufficiently described in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) aims to describe the epidemiology, molecular characterization, and antimicrobial susceptibility of outpatient CDI across Canada. Methods: Epidemiologic data were collected from patients diagnosed with CDI from a network of 47 adult and pediatric CNISP hospitals. Patients presenting to an outpatient setting such as the ED or outpatient clinics were considered as outpatient CDI. Cases were considered HAIs if the patient had had a healthcare intervention within the previous 4 weeks, and they were considered community-associated if there was no history of hospitalization within the previous 12 weeks. Clostridioides difficile isolates were submitted to the National Microbiology Laboratory for testing during an annual 2-month targeted surveillance period. National and regional rates of CDI were stratified by outpatient location. Results: Between January 1, 2015, and June 30, 2019, 2,691 cases of outpatient-CDI were reported, and 348 isolates were available for testing. Most cases (1,475 of 2,691, 54.8%) were identified in outpatient clinics, and 72.8% (1,960 of 2,691) were classified as community associated. CDI cases per 100,000 ED visits were highest in 2015, at 10.3, and decreased to 8.1 in 2018. Rates from outpatient clinics decreased from 3.5 in 2016 to 2.7 in 2018 (Fig. 1). Regionally, CDI rates in the ED declined in Central Canada and increased in the West after 2016. Rates in outpatient clinics were >2 times higher in the West compared to other regions. RT027 associated with NAP1 was most common among ED patients (26 of 195, 13.3%), whereas RT106 associated with NAP11 was predominant in outpatient clinics (22 of 189, 11.6%). Overall, 10.4% of isolates were resistant to moxifloxacin, 0.5% were resistant to rifampin, and 24.2% were resistant to clindamycin. No resistance was observed for metronidazole, vancomycin, or tigecycline. Compared to CNISP inpatient CDI data, outpatients with CDI were younger (51.8 ± 23.3 vs 64.2 ± 21.6; P < .001), included more females (56.4% vs 50.9%; P < .001), and were more often treated with metronidazole (63.0% vs 56.1%; P < .001). Conclusions: For the first time, CDI cases identified in outpatient settings were characterized in a Canadian context. Outpatient CDI rates are decreasing overall, but they vary by region. Predominant ribotypes vary based on outpatient location. Outpatients with CDI are younger and are more likely female than inpatients with CDI.

Funding: None

Disclosures: Susy Hota reports contract research for Finch Therapeutics.

Background: Carbapenemase-producing Enterobacterales (CPE) have rapidly become a global health concern and are associated with substantial morbidity and mortality due to limited treatment options. Travel to endemic areas, especially healthcare exposure in these areas, is an important risk factor for acquisition. We describe the evolving epidemiology, molecular features, and outcomes of CPE in Canada through surveillance by the Canadian Nosocomial Infection Surveillance Program (CNISP). Methods: CNISP has conducted surveillance for CPE among inpatients and outpatients of all ages since 2010. Participating acute-care facilities submit eligible specimens to the National Microbiology Laboratory for detection of carbapenemase production, and epidemiological data are collected. Incidence rates per 10,000 patient days are calculated based on inpatient data. Results: In total, 59 CNISP hospitals in 10 Canadian provinces representing 21,789 beds and 6,785,013 patient days participated in this surveillance. From 2010 to 2018, 118 (26%) CPE-infected and 547 (74%) CPE-colonized patients were identified. Few pediatric cases were identified (n = 18). Infection incidence rates remain low and stable (0.02 per 10,000 patient days in 2010 to 0.03 per 10,000 patient days in 2018), and colonization incidence rates have increased by 89% over the surveillance period. Overall, 92% of cases were acquired in a healthcare facility: 61% (n = 278) in a Canadian healthcare facility and 31% (n = 142) in a healthcare facility outside Canada. Of the 8% of cases not acquired in a healthcare facility, 50% (16 of 32) reported travel outside of Canada in the 12 months prior to positive culture. The distribution of carbapenemases varied by region; New Delhi metallo-B-lactamase (NDM) was dominant (59%) in western Canada and Klebsiella pneumoniae carbapenemase (KPC) (66%) in central Canada. NDM and class D carbapenemase OXA-48 were more commonly identified among those who traveled outside of Canada, whereas KPC was more commonly identified among patients without travel. In addition, 30-day all-cause mortality was 14% (25 of 181) among CPE infected patients and 32% (14 of 44) among those with bacteremia. Conclusions: CPE rates remain low in Canada; however, national surveillance data suggest that the increase in CPE in Canada is now being driven by local nosocomial transmission as well as travel and healthcare within endemic areas. Changes in screening practices may have contributed to the increase in colonizations; however, these data are currently lacking and will be collected moving forward. These data highlight the need to intensify surveillance and coordinate infection control measures to prevent further spread of CPE in Canadian acute-care hospitals.

Funding: None

Disclosures: Susy Hota reports contracted research for Finch Therapeutics. Allison McGeer reports funds to her institution for projects for which she is the principal investigator from Pfizer and Merck, as well as consulting fees from the following companies: Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.

Worldwide, cardiovascular disease (CVD) is the number 1 cause of mortality and is associated with insulin resistance (IR). Emerging biomarkers such as FGF21 and adiponectin are associated with cardiometabolic risk. Low carbohydrate, high fat (LCHF) diets have been reported to reduce cardiometabolic risk markers; however, few studies have compared a LCHF diet vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on adiponectin and FGF21. The purpose of this study was to investigate the effects of an ad libitum LCHF vs. HC diet on IR, FGF21 and adiponectin in 16 healthy adults. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants were randomly assigned to a HC diet (n = 8, the UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) or a LCHF diet (n = 8, consume < 50 g/day of carbohydrates). All provided plasma samples at 0, 4 and 8 weeks. FGF21 (R&D Systems) was analysed via ELISA and adiponectin, insulin and glucose were analysed via immunoassay technology (Randox Evidence Investigator™ Metabolic Syndrome Arrays I & II). Mann Whitney, Friedmans, Wilcoxon tests and 2×3 ANOVA (IBM SPSS 25®) were undertaken to investigate significant differences between and within groups. The homeostatic model assessment (HOMA) was used to calculate IR. FGF21 significantly (P = 0.04) decreased (Mdn, IQR:148.16, 78.51–282.02 to 99.4, 39.87–132.29 pg/ml) after 4 weeks and significantly (P = 0.02) increased (Mdn, IQR:167.38, 80.82–232.89 pg/ml) by 8 weeks vs. baseline with LCHF. No significant differences (P > 0.05) were observed between groups. Adiponectin was significantly (P = 0.03) different at week 4 only between groups. Adiponectin increased after 4 weeks (Mdn, IQR:13.44, 9.12–25.47 to 16.64, 11.96–21.51 ng/ml) but was only significantly (P = 0.03) different by 8 weeks vs. baseline in the HC group (Mdn, IQR:16, 10.8–27.43 ng/ml). Adiponectin remained unchanged (P = 0.96) in the LCHF group. HOMA significantly decreased with both diets after 8 weeks only (mean ± SD, LCHF: 2.9 ± 1.3 to 1.8 ± 0.8, HC: 2.5 ± 0.6 to 1.9 ± 0.6, P = 0.008) but was not significantly (P = 0.60) different between groups. These preliminary data reveal that while both diets improved insulin sensitivity, they may do so by different mechanisms. Future studies are warranted to investigate further, how a LCHF vs. HC diet affects FGF21 and adiponectin, and the subsequent regulation of IR. Furthermore, studies that extend these findings by determining the impact of LCHF vs. HC on peripheral metabolism to determine potential nutrition-mediated mechanisms of metabolic adaptation are warranted.

Apolipoproteins (apo) regulate lipoprotein characteristics and lipid metabolism. ApoC-III is a regulator of triglyceride-rich lipoprotein (TRL) metabolism and apolipoproteins are important biomarkers for cardiovascular disease (CVD) risk prediction. A low carbohydrate high fat (LCHF) diet improves cardiometabolic risk, especially via reduction of TRL. However, few studies have compared a LCHF vs. a high carbohydrate (HC), lower fat diet under ad libitum conditions on apoC-III levels. The objectives of this investigation were to measure the effect of a LCHF vs. a HC diet on apoC-III, apoA1, apoB and apoB/apoA1 in 16 healthy Caucasian adults aged 19–64. Ethical approval: Liverpool John Moores University Research Ethics Committee (16/ELS/029); registered with ClinicalTrials.gov (Ref. NCT03257085). Participants randomly assigned to a HC diet (UK Eatwell guidelines; ≥ 50% of energy from carbohydrates) (n = 8), or a LCHF diet (consume < 50 g/day of carbohydrates) (n = 8) provided plasma samples at 0, 4 and 8 weeks. ApoA1 and apoB were analysed by an automated chemistry analyser (Daytona, Randox Laboratories Ltd, UK). ApoC-III was analysed via ELISA (Thermo Fisher Ltd, USA). Factorial 2×3 ANOVA and ANCOVA (IBM SPSS 25®) were undertaken to investigate significant differences and to control for variables influenced by baseline measures and visceral adipose tissue (VAT). Results show 0, 4, and 8 weeks respectively: ApoC-III (LCHF: 19.12 ± 9.14, 16.05 ± 7.95, 15.11 ± 3.17 mg/dl; HC: 22.13 ± 8.38, 28.22 ± 13.85, 22.22 ± 7.7 mg/dl) showed no significant (P = 0.319) change. No significant (P = 0.23) change was also observed in ApoB (LCHF: 107.25 ± 20.35, 111.38 ± 24.81, 111.43 ± 19.93 mg/dl; HC: 94.38 ± 20.79, 105.00 ± 20.13, 99.00 ± 29.09 mg/dl). Similarly apoA1 (LCHF: 158.71 ± 14.27, 166.50 ± 23.09, 173.00 ± 29.42 mg/dl; HC: 164.71 ± 30.25, 172.50 ± 29.44, 174.00 ± 32.83 mg/dl) showed no significant change (P = 0.76). This resulted in a relatively unchanged apoB/A1 throughout the study in both diets (P = 0.30). No significant (P > 0.05) differences were found after 4 weeks or between groups also. ANCOVA revealed a trend (P = 0.06) in apoC-III for a difference between groups (LCHF: Δ-6.6 mg/dl vs. HC: Δ1.2 mg/dl) after 8 weeks but no significant (P > 0.05) changes in other apolipoproteins were detected. These preliminary data reveal that a LCHF diet does not improve the apolipoprotein profile; however, when accounting for other metabolic risk factors (i.e. VAT) there was a trend towards lowering apoC-III levels (P = 0.06). Modulation of apoC-III may lead to improved lipid metabolism, but higher-powered studies are warranted before any improvement on CVD risk can be inferred.

Our recent study (1) showed that the amount of dietary carbohydrates in obesity interventions has differential effects on cardiovascular risk markers (CVM) and effects magnitude depends on intervention duration. Very-low carbohydrate high-fat diets (VLCD) were superior in ameliorating lipid markers compared to high-carbohydrate low-fat diets (LFD).

We updated our systematic review and meta-analysis to include long-term effects of VLCD (< 50 g /day) on weight, glucose, total cholesterol, insulin and blood pressure (BP) among overweight/obese adults in comparison to LFD.

Medline, PubMed, Cochrane Central, and CINAHLPlus were searched to identify large (n > 100) randomised controlled trials (RCT) with duration ≥ 6 months. Risk of bias, a random effects model and subgroup analyses based on duration of follow-up were performed using Review Manager. Results were reported according to PRISMA.

Four open label RCT (n = 723; 362 VLCD; 361 LFD) with some form of behavioral intervention and duration 6–24 months were identified. VLCD showed more favorable effects on diastolic BP at 6 months (-1.96; 95%CI, -2.99 to 00.93; P = 0.0002) and 24 months (-2.69; 95%CI, -4.87 to -0.51; P = 0.001), near significant level at 12 months (-1.79; 95%CI, -3.56 to 0.04; P = 0.05) and an overall total favourable effect (-1.98; 95%CI, -2.73 to -1.22). The decrease in systolic BP was greater among VLCD for the whole period and the overall total effect reached the level of significance (-1.76; 95%CI, -3.56 to 0.04; P = 0.05). VLCD showed beneficial effect on total cholesterol level at 6 and 12 months (-0.01 mmol/L; 95%CI, -0.01 to –0.00; P = 0.002 and -0.01 mmol/L; 95%CI, -0.01 to –0.00; P = 0.005, respectively). The mean changes in weight, and fasting glucose and insulin levels revealed non-significant differences between both diets at any measured time, although these parameters decreased within both groups compared to baseline.

VLCD led to significant total weighted mean decrease of diastolic BP and near significant decrease of systolic BP independent of changes in body weight, fasting glucose or insulin levels. The present data on decreased levels of diastolic BP and total cholesterol, combined with our recently published results on increased HDL-cholesterol, decreased triglycerides and no significant effect on LDL-cholesterol (1) provide evidence that VLCD are superior to LFD in improving traditional CVM in longer term.

We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from $z = 0.35$ to 3; and a deep, high-redshift HI IM survey over 100 deg2 from $z = 3$ to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to $z \sim 3$ with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to $z = 6$ . These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.